title: Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation.
abstract: The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-α, peroxisome proliferator-activated receptor-γ coactivator-1α), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Lettieri Barbato
authors.forename: K
authors.initials: K
authors.lastname: Aquilano
authors.forename: S
authors.initials: S
authors.lastname: Baldelli
authors.forename: S M
authors.initials: SM
authors.lastname: Cannata
authors.forename: S
authors.initials: S
authors.lastname: Bernardini
authors.forename: G
authors.initials: G
authors.lastname: Rotilio
authors.forename: M R
authors.initials: MR
authors.lastname: Ciriolo
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D004032:Diet; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007249:Inflammation; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011394:Proline Oxidase / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D000217:Acyltransferases
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D008049:Lipase; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011394:Proline Oxidase; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C467200:Foxo1 protein, mouse; C485290:Ppargc1a protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases